Laboratoire d’Oncologie moléculaire, Pôle Biologie Santé, 40, avenue du Recteur‐Pineau, 86021 Poitiers
Recent works aimed at clarifying the respective roles of p16
INKa and p14
ARF (both located on the same INK4a locus on chromosome 9p21 in man) in malignant transformation come to the conclusion that p16
INK4a is the true tumor suppressor gene in man. In mouse, it is the p19
ARF knockout that suppresses the barrier protecting cells from malignant transformation. This situation is in agreement with p19
ARF‐ and p16‐mediated senescence induced by oncogenic mutated ras (Ras*) in mouse and man respectively. Other results have shown that senescence in human diploid fibroblasts is associated with heterochromatin occurrence that maintains in repressed state E2F1‐induced gens required for G
1 to S phases transition. Since RB protein is responsible for this chromatin modification, cells with any impaired RB pathway cannot enter into senescence.